The Molecular Biology Core is designed to expedite access to basic molecular biology techniques, resources, and training needed by investigators exploring problems in HIV replication, pathogenesis, therapy, and immunoprophylaxis. A particular emphasis, is the support of developmental projects and investigators just entering the field of HIV research. The Core has four specific objectives: (1) The Core supports research requiring RNA and DMA sequence information. Low-cost, rapid, accurate DNA sequencing is provided, along with special expertise in sequencing of HIV-1, HIV-2, SIV, and other lentiviruses. Training in preparation and sequencing for custom applications, and optimization of sequencing under specialized conditions for requested projects is supported. (2) The Core supports other aspects of molecular biology research. This includes amplification and hybridization techniques for detection and quantification (plasma, tissue and culture samples) for AIDS-related viruses and vectors including HIV-1, HIV-2, SIV, EBV, KSHV, and HCV viruses, as well as MuLV-, HIV-1-, HIV-2-, and FIV-based vectors. (3) The Core provides support for gene-silencing technology. This includes siRNA design, synthesis, and vector construction, as well as lentiviral vectors for siRNA/shRNA expression. (4) The Core supports other aspects of molecular biology needed for HIV research. This includes distribution of specialty reagents (primers, plasmids, maps, other) and assistance with design of projects involving PCR and/or cloning. The Core also supports training seminars, and provides one-on-one training for fellows and students in sequencing techniques, methods, and techniques related to miRNA and siRNA, and QC and kinetic real-time PCR. Mentoring is provided to developmental investigators. In addition, the Core assists in acquisition, support, and administration of computational infrastructure, and facilitates access to third-party molecular biology software needed by HIV/AIDS investigators. Past and ongoing molecular biology support of UCSD research efforts illustrates the Core's usefulness. Since the last competitive renewal in 2002, work performed by the Molecular Biology Core has been identified by 111 different investigators who have used the Core in generating 92 publications and 40 new or renewal grant applications. Research efforts supported by the Core have increased our understanding of viral resistance, viral variation and compartmentalization, the immunopathogenesis of disease, and new approaches for treatment and immunoprophylaxis. In summary, the Molecular Biology Core is a valuable, productive, and popular core resource for the UCSD CFAR.